{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:34:37Z","timestamp":1788273277386,"version":"build-2803163510"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.15502.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000}}],"reference-count":61,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oxford University Clinical Research Unit","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>Hyponatremia is the commonest electrolyte abnormality in hospitalized patients and is associated with poor outcome. Hyponatremia is categorized on the basis of serum sodium into severe (&lt; 120 mEq\/L), moderate (120-129 mEq\/L) and mild (130-134mEq\/L) groups. Serum sodium has an important role in maintaining serum osmolality, which is maintained by the action of antidiuretic hormone (ADH) secreted from the posterior pituitary, and natriuretic peptides such as atrial natriuretic peptide and brain natriuretic peptide. These peptides act on kidney tubules via the renin angiotensin aldosterone system. Hyponatremia &lt;120mEq\/L or a rapid decline in serum sodium can result in neurological manifestations, ranging from confusion to coma and seizure. Cerebral salt wasting (CSW) and syndrome of inappropriate secretion of ADH (SIADH) are important causes of hyponatremia in tuberculosis meningitis (TBM). CSW is more common than SIADH. The differentiation between CSW and SIADH is important because treatment of one may be detrimental for the other; evidence of hypovolemia in CSW and euvolemia or hypervolemia in SIADH is used for differentiation. In addition, evidence of dehydration, polyuria, negative fluid balance as assessed by intake output chart, weight loss, laboratory evidence and sometimes central venous pressure are helpful in the diagnosis of these disorders. Volume contraction in CSW may be more protracted than hyponatremia and may contribute to border zone infarctions in TBM. Hyponatremia should be promptly and carefully treated by saline and oral salt, while 3% saline should be used in severe hyponatremia with coma and seizure. In refractory patients with hyponatremia, fludrocortisone helps in early normalization of serum sodium without affecting polyuria or functional outcome. In SIADH, V2 receptor antagonist conivaptan or tolvaptan may be used if the patient is not responding to fluid restriction. Fluid restriction in SIADH has not been found to be beneficial in TBM and should be avoided.<\/ns3:p>","DOI":"10.12688\/wellcomeopenres.15502.2","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T15:25:08Z","timestamp":1617031508000},"page":"189","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Mechanism, spectrum, consequences and management of hyponatremia in tuberculous meningitis"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7317-957X","authenticated-orcid":false,"given":"Usha K.","family":"Misra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayantee","family":"Kalita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Tuberculous Meningitis International Research 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death","year":"2013"}],"container-title":["Wellcome Open 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16964.r37864, Praveen Kumar Sharma, Department of Neurology, King George Medical University (KGMU), Lucknow, Uttar Pradesh, India, 24 Feb 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-189\/v1#referee-response-37864","order":0,"name":"referee-response-37864","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>USHA KANT MISRA<\/b>; \n<i>Posted: 11 Feb 2021<\/i>; Dear Sir, The above-mentioned changes have been included in the revised version and resubmitted for publication in your esteemed journal. &nbsp;  elaboration of the mixed cause and strategy of its management should have been included as well.  \n<b>Answer:<\/b> The miscellaneous causes refer to other causes of hyponatremia and our comments are targeted to clearly defined cases. Using our criteria we feel that a clear diagnosis is possible. However some authors have emphasized that it is difficult to differentiate these conditions clearly and they suggest the term salt wanting syndrome&nbsp;&nbsp; and treat it with saline when in doubt.  Exclusion of endocrine dysfunction is important for the diagnosis of both CSW and SIADH. Here I wish to add since endocrine dysfunction is not uncommon in TBM and can be central in origin, Hypercortisolism and Hypothyroidism which can cause hypo-osmolar hyponatremia, should have been stressed upon for the exclusion with appropriate tests .  \n<b>Answer:<\/b> We agree that endocrinal disorders should be excluded before diagnosis of CSW and SIADH. If present these have to be managed as usual.  Suggest including fractional excretion of Urate as lab support for the diagnosis of SIADH since the criteria given here for its diagnosis are fine in a clearly hypervolemic patient but become confusing in euvolemic mildly hypervolemic cases  \n<b>Answer:<\/b> Serum uric acid is likely to be low in SIADH and normal or high in CSW. This relationship has, however, not been well studied. In a study, serum uric acid was unexpectedly low in CSW.3 Hyponatremia and high urate excretion might be a common feature of intracranial disease in general (Maesaka et al 1998 )","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-189\/v2#referee-comment-4528","order":1,"name":"referee-comment-4528","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16964.r38779, Ghulamullah Lail, Department of Medicine and Allied, Jinnah Medical and Dental College, Karachi, Pakistan, 20 Jul 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-189\/v1#referee-response-38779","order":2,"name":"referee-response-38779","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>USHA KANT MISRA<\/b>; \n<i>Posted: 11 Feb 2021<\/i>; Dear Sir, The above-mentioned changes have been included in the revised version and resubmitted for publication in your esteemed journal.  \n<b>Ghulamullah Lail<\/b>  Fluid restriction and Vaptans&nbsp;in SIADH in TBM.  \n<b>Answer:<\/b> In our experience CSW is much more common than SIADH. In view of hazards of fluid restriction in meningitis, we feel that the patients should be treated with hypertonic saline during emergency which may be followed by normal saline and salt. If one is very sure of the diagnosis, vaptans may be used but in our experience it is not common. We have included discussion on vaptans in the paper.&nbsp;  Diagnostic criteria for SIADH may be adjusted as more than 30mmol\/l (J AmSocNephrol 28: 1340\u20131349, 2017 ) higher urate clearance observed during hyponatremia related to SIADH (CJASN July2008, 3 (4) 1175-1184)  \n<b>Answer:<\/b> We have kept the diagnosis of CSW and SIADH based on simple bedside criteria avoiding lab estimations which may not be widely available. We agree that the utility of our criteria need to be confirmed&nbsp; by other investigators.  No reference given for saline infusion test.  \n<b>Answer:<\/b> In SIDAH, hyponatremia is aggravated by infusing 100 mL of normal saline, whereas it leads to normalization of serum sodium in CSW. Similarly, 20 mg of furosemide may normalize serum sodium in SIADH but not in CSW.5 However, the safety or reproducibility of these tests has not been validated. Hence, we have not used saline infusion test (Casulari et al 2004)","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-189\/v2#referee-comment-4527","order":3,"name":"referee-comment-4527","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust through funding to the Tuberculous Meningitis International Research Consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}